RESUMEN
O presente trabalho se valeu de células de hepatoma humano Hep G2 para estudar se existe algum efeito das vastatinas sobre a atividade das enzimas que governam a hidrólise hepática do coleterol: colesterol éster hidrolases lisossomal, citosólica e microssomal. As enzimas foram incubadas com ou sem amostras de vastatina, dissovidas em dimetilsulfóxido. A adiçao das vastatinas ofereceu distintos resultados, conforme a maneira que se apresentou o substrato às enzimas. No caso da colesterol éster hidrolase lisossomal, obteve-se inibiçao em substrato Hajjar, com sais biliares, e estimulaçao em substrato Brecher, desprovido de sais biliares. A hidrolase citosólica teve sua atividade inibida em substrato Hajjar e constante em substrato Brecher.
Asunto(s)
Hepatoblastoma/enzimología , Hidrolasas/análisis , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Neoplasias Hepáticas/enzimología , Esterol Esterasa/efectos de los fármacos , Fracciones Subcelulares/enzimología , Células Tumorales CultivadasRESUMEN
We had previously reported that juvenile hormone III (JH III) and the JH analogue 2-(4-phenoxy phenoxy)-ethoxytetrahydropyran exert inhibitory effects on progesterone synthesis by blocking cAMP production in hCG-stimulated MA-10 Leydig tumor cells. In the present study, the effects of JH analogue upon the biosynthetic pathway of progesterone synthesis have been examined. Our results demonstrated that JH analogue inhibited progesterone production even in the presence of 20-hydroxycholesterol or 25-hydroxycholesterol. Furthermore, although JH analogue inhibited pregnenolone production in hCG-stimulated MA-10 cells the activity of the 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) was unaffected. These data suggest that JH analogue might inhibit the steroidogenic pathway in Leydig tumor cells by inhibiting the activity of the cholesterol side chain cleavage (CSCC) enzymatic complex. The JH analogue was also evaluated for inhibitory actions on cholesterol availability. An important effect of this compound was the interference with the cellular process of plasma membrane cholesterol internalization. Moreover, JH analogue inhibited not only the use of cholesterol ester for steroid biosynthesis under Bt2cAMP stimulation, but also the cholesterol ester hydrolase (CEH) activity in MA-10 Leydig tumor cells.